Skip to main content

Avenues for Further Research

  • Chapter
  • First Online:
Diagnostic Meta-Analysis

Abstract

In this chapter, we present an overview of the recent statistical methods for diagnostic meta-analysis and suggest a few directions for future research. We discuss two important issues regarding (a) the robustness of model misspecifications and (b) the identifiability of models and the assumption of conditional independence in the absence of a gold standard. With increasing availability of biomedical data, the individual patient-level data meta-analyses offer new insights into evidence synthesis compared to traditional aggregated data-based meta-analyses. In particular, the approaches to combine individual patient-level data with aggregated data can inform personalized medical decision based on patient-level characteristics and help to identify clinically relevant subgroups. However, such integration methods for diagnostic prediction research are limited, and hence there is a growing need for developing of novel statistical methods that can address potential issues including model validation, missing predictors, and between-studies heterogeneity while combining both types of data. Despite the perceived advantages of individual patient-level data, using individual patient-level data alone may still encounter a number of challenges, such as partial verification bias and the absence of a gold standard. We discuss these challenges by two examples.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

GLMMs:

Generalized linear mixed models

HSROC:

Hierarchical summary receiver operating characteristic

IPD:

Individual patient-level data

MRI:

Magnetic resonance imaging

NPV:

Negative predictive value

PPV:

Positive predictive value

ROP:

Retinopathy of prematurity

SROC:

Summary receiver operating characteristic

References

  1. Reitsma JB, Glas AS, Rutjes AW, Scholten RJ, Bossuyt PM, Zwinderman AH. Bivariate analysis of sensitivity and specificity produces informative summary measures in diagnostic reviews. J Clin Epidemiol. 2005;58:982–90.

    Article  PubMed  Google Scholar 

  2. Littenberg B, Moses LE. Estimating diagnostic accuracy from multiple conflicting reports: a new meta-analytic method. Med Decis Mak. 1993;13:313–21.

    Article  CAS  Google Scholar 

  3. Moses LE, Shapiro D, Littenberg B. Combining independent studies of a diagnostic test into a summary ROC curve: data-analytic approaches and some additional considerations. Stat Med. 1993;12:1293–316.

    Article  CAS  PubMed  Google Scholar 

  4. Walter S. Properties of the summary receiver operating characteristic (SROC) curve for diagnostic test data. Stat Med. 2002;21:1237–56.

    Article  CAS  PubMed  Google Scholar 

  5. Arends L, Hamza TH, van Houwelingen JC, Heijenbrok-Kal MH, Hunink MG, Stijnen T. Bivariate random effects meta-analysis of ROC curves. Med Decis Mak. 2008;28:621–38.

    Article  CAS  Google Scholar 

  6. Van Houwelingen HC, Arends LR, Stijnen T. Advanced methods in meta-analysis: multivariate approach and meta-regression. Stat Med. 2002;21:589–624.

    Article  PubMed  Google Scholar 

  7. Van Houwelingen HC, Zwinderman KH, Stijnen T. A bivariate approach to meta-analysis. Stat Med. 1993;12:2273–84.

    Article  PubMed  Google Scholar 

  8. Chu H, Cole SR. Bivariate meta-analysis of sensitivity and specificity with sparse data: a generalized linear mixed model approach. J Clin Epidemiol. 2006;59:1331–2.

    Article  PubMed  Google Scholar 

  9. Hamza TH, van Houwelingen HC, Stijnen T. The binomial distribution of meta-analysis was preferred to model within-study variability. J Clin Epidemiol. 2008;61:41–51.

    Article  PubMed  Google Scholar 

  10. Harbord RM, Deeks JJ, Egger M, Whiting P, Sterne JA. A unification of models for meta-analysis of diagnostic accuracy studies. Biostatistics. 2007;8:239–51.

    Article  PubMed  Google Scholar 

  11. Chen Y, Liu Y, Ning J, Cormier J, Chu H. A hybrid model for combining case–control and cohort studies in systematic reviews of diagnostic tests. J R Stat Soc Ser C Appl Stat. 2015;64:469–89.

    Article  PubMed  Google Scholar 

  12. Lindsay BG. Composite likelihood methods. Contemp Math. 1988;80:221–39.

    Article  Google Scholar 

  13. Chen Y, Liu Y, Ning J, Nie L, Zhu H, Chu H. A composite likelihood method for bivariate meta-analysis in diagnostic systematic reviews. Stat Methods Med Res. 2017;26:914–30.

    Article  PubMed  Google Scholar 

  14. Feinstein A. Misguided efforts and future challenges for research on “diagnostic tests”. J Epidemiol Community Health. 2002;56:330–2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Leeflang MM, Rutjes AW, Reitsma JB, Hooft L, Bossuyt PM. Variation of a test’s sensitivity and specificity with disease prevalence. Can Med Assoc J. 2013;185:E537–44.

    Article  Google Scholar 

  16. Chu H, Nie L, Cole SR, Poole C. Meta-analysis of diagnostic accuracy studies accounting for disease prevalence: alternative parameterizations and model selection. Stat Med. 2009;28:2384–99.

    Article  PubMed  Google Scholar 

  17. Ma X, Chen Y, Cole SR, Chu H. A hybrid Bayesian hierarchical model combining cohort and case–control studies for meta-analysis of diagnostic tests: accounting for partial verification bias. Stat Methods Med Res. 2016;25:3015–37.

    Article  PubMed  Google Scholar 

  18. Chen Y, Liu Y, Chu H, Ting Lee ML, Schmid CH. A simple and robust method for multivariate meta-analysis of diagnostic test accuracy. Stat Med. 2017;36:105–21.

    Article  PubMed  Google Scholar 

  19. Joseph L, Gyorkos TW, Coupal L. Bayesian estimation of disease prevalence and the parameters of diagnostic tests in the absence of a gold standard. Am J Epidemiol. 1995;141:263–72.

    Article  CAS  PubMed  Google Scholar 

  20. Rutjes AW, Reitsma JB, Di Nisio M, Smidt N, van Rijn JC, Bossuyt PM. Evidence of bias and variation in diagnostic accuracy studies. Can Med Assoc J. 2006;174:469–76.

    Article  Google Scholar 

  21. Chu H, Chen S, Louis TA. Random effects models in a meta-analysis of the accuracy of two diagnostic tests without a gold standard. J Am Stat Assoc. 2009;104:512–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Dendukuri N, Schiller I, Joseph L, Pai M. Bayesian meta-analysis of the accuracy of a test for tuberculous pleuritis in the absence of a gold standard reference. Biometrics. 2012;68:1285–93.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Liu Y, Chen Y, Chu H. A unification of models for meta-analysis of diagnostic accuracy studies without a gold standard. Biometrics. 2015;71:538–47.

    Article  PubMed  Google Scholar 

  24. Alonzo TA, Pepe MS. Using a combination of reference tests to assess the accuracy of a new diagnostic test. Stat Med. 1999;18:2987–3003.

    Article  CAS  PubMed  Google Scholar 

  25. Naaktgeboren CA, Bertens LC, van Smeden M, de Groot JA, Moons KG, Reitsma JB. Value of composite reference standards in diagnostic research. BMJ. 2013;347:f5605.

    Article  PubMed  Google Scholar 

  26. Qu Y, Tan M, Kutner MH. Random effects models in latent class analysis for evaluating accuracy of diagnostic tests. Biometrics. 1996;52:797–810.

    Article  CAS  PubMed  Google Scholar 

  27. Hui SL, Zhou XH. Evaluation of diagnostic tests without gold standards. Stat Methods Med Res. 1998;7:354–70.

    Article  CAS  PubMed  Google Scholar 

  28. Pepe MS, Alonzo TA. Comparing disease screening tests when true disease status is ascertained only for screen positives. Biostatistics. 2001;2:249–60.

    Article  CAS  PubMed  Google Scholar 

  29. Albert PS, Dodd LE. A cautionary note on the robustness of latent class models for estimating diagnostic error without a gold standard. Biometrics. 2004;60:427–35.

    Article  PubMed  Google Scholar 

  30. Gustafson P, et al. On model expansion, model contraction, identifiability and prior information: two illustrative scenarios involving mismeasured variables [with comments and rejoinder]. Stat Sci. 2005;20:111–40.

    Article  Google Scholar 

  31. Hui SL, Walter SD. Estimating the error rates of diagnostic tests. Biometrics. 1980;36:167–71.

    Article  CAS  PubMed  Google Scholar 

  32. Pepe MS, Janes H. Insights into latent class analysis of diagnostic test performance. Biostatistics. 2006;8:474–84.

    Article  PubMed  Google Scholar 

  33. Dendukuri N, Joseph L. Bayesian approaches to modeling the conditional dependence between multiple diagnostic tests. Biometrics. 2001;57:158–67.

    Article  CAS  PubMed  Google Scholar 

  34. Lambert PC, et al. A comparison of summary patient-level covariates in meta-regression with individual patient data meta-analysis. J Clin Epidemiol. 2002;55:86–94.

    Article  CAS  PubMed  Google Scholar 

  35. Berlin JA, Santanna J, Schmid CH, Szczech LA, Feldman HI, Anti-Lymphocyte Antibody Induction Therapy Study Group. Individual patient-versus group-level data meta-regressions for the investigation of treatment effect modifiers: ecological bias rears its ugly head. Stat Med. 2002;21:371–87.

    Article  PubMed  Google Scholar 

  36. Thompson SG, Higgins J. How should meta-regression analyses be undertaken and interpreted? Stat Med. 2002;21:1559–73.

    Article  PubMed  Google Scholar 

  37. Schmid CH, Stark PC, Berlin JA, Landais P, Lau J. Meta-regression detected associations between heterogeneous treatment effects and study-level, but not patient-level, factors. J Clin Epidemiol. 2004;57:683–97.

    Article  PubMed  Google Scholar 

  38. Riley RD, Lambert PC, Abo-Zaid G. Meta-analysis of individual participant data: rationale, conduct, and reporting. BMJ. 2010;340:c221.

    Article  PubMed  Google Scholar 

  39. Smith CT, Williamson PR, Marson AG. Investigating heterogeneity in an individual patient data meta-analysis of time to event outcomes. Stat Med. 2005;24:1307–19.

    Article  PubMed  Google Scholar 

  40. Steinberg K, Smith SJ, Stroup DF, Olkin I, Lee NC, Williamson GD, Thacker SB. Comparison of effect estimates from a meta-analysis of summary data from published studies and from a meta-analysis using individual patient data for ovarian cancer studies. Am J Epidemiol. 1997;145:917–25.

    Article  CAS  PubMed  Google Scholar 

  41. Higgins JP, Green S. Cochrane handbook for systematic reviews of interventions, vol. 4. Chichester: John Wiley & Sons; 2011.

    Google Scholar 

  42. Thompson SG, Higgins JP. Can meta-analysis help target interventions at individuals most likely to benefit? Lancet. 2005;365:341–6.

    Article  PubMed  Google Scholar 

  43. Riley RD, Steyerberg EW. Meta-analysis of a binary outcome using individual participant data and aggregate data. Res Synth Methods. 2010;1:2–19.

    Article  PubMed  Google Scholar 

  44. Sutton AJ, Kendrick D, Coupland CA. Meta-analysis of individual-and aggregate-level data. Stat Med. 2008;27:651–69.

    Article  CAS  PubMed  Google Scholar 

  45. Riley RD, Dodd SR, Craig JV, Thompson JR, Williamson PR. Meta-analysis of diagnostic test studies using individual patient data and aggregate data. Stat Med. 2008;27:6111–36.

    Article  PubMed  Google Scholar 

  46. Steyerberg EW, Mushkudiani N, Perel P, Butcher I, Lu J, McHugh GS, Murray GD, Marmarou A, Roberts I, Habbema JD, Maas AI. Predicting outcome after traumatic brain injury: development and international validation of prognostic scores based on admission characteristics. PLoS Med. 2008;5:e165.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Collins GS, Reitsma JB, Altman DG, Moons KG. Transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD): the TRIPOD statement. BMC Med. 2015;13:1.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Riley RD, Ensor J, Snell KI, Debray TP, Altman DG, Moons KG, Collins GS. External validation of clinical prediction models using big datasets from e-health records or IPD meta-analysis: opportunities and challenges. BMJ. 2016;353:i3140.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Ahmed I, Debray TP, Moons KG, Riley RD. Developing and validating risk prediction models in an individual participant data meta-analysis. BMC Med Res Methodol. 2014;14:3.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Steyerberg EW, Eijkemans MJ, Van Houwelingen JC, Lee KL, Habbema JD. Prognostic models based on literature and individual patient data in logistic regression analysis. Stat Med. 2000;19:141–60.

    Article  CAS  PubMed  Google Scholar 

  51. Debray TP, Koffijberg H, Lu D, Vergouwe Y, Steyerberg EW, Moons KG. Incorporating published univariable associations in diagnostic and prognostic modeling. BMC Med Res Methodol. 2012;12:121.

    Article  PubMed  Google Scholar 

  52. Greenland S. Quantitative methods in the review of epidemiologic literature. Epidemiol Rev. 1987;9:1–30.

    Article  CAS  PubMed  Google Scholar 

  53. Debray T, Koffijberg H, Vergouwe Y, Moons KG, Steyerberg EW. Aggregating published prediction models with individual participant data: a comparison of different approaches. Stat Med. 2012;31:2697–712.

    Article  PubMed  Google Scholar 

  54. Cook NR. Use and misuse of the receiver operating characteristic curve in risk prediction. Circulation. 2007;115:928–35.

    Article  PubMed  Google Scholar 

  55. Steyerberg EW, Vickers AJ, Cook NR, Gerds T, Gonen M, Obuchowski N, Pencina MJ, Kattan MW. Assessing the performance of prediction models: a framework for some traditional and novel measures. Epidemiology. 2010;21:128–38.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Debray T, Moons KG, Ahmed I, Koffijberg H, Riley RD. A framework for developing, implementing, and evaluating clinical prediction models in an individual participant data meta-analysis. Stat Med. 2013;32:3158–80.

    Article  PubMed  Google Scholar 

  57. Debray TP, Riley RD, Rovers MM, Reitsma JB, Moons KG, Cochrane IPD Meta-analysis Methods Group. Individual participant data (IPD) meta-analyses of diagnostic and prognostic modeling studies: guidance on their use. PLoS Med. 2015;12:e1001886.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Rockall A, Meroni R, Sohaib SA, Reynolds K, Alexander-Sefre F, Shepherd JH, Jacobs I, Reznek RH. Evaluation of endometrial carcinoma on magnetic resonance imaging. Int J Gynecol Cancer. 2007;17:188–96.

    Article  CAS  PubMed  Google Scholar 

  59. Saez F, Urresola A, Larena JA, Martín JI, Pijuán JI, Schneider J, Ibáñez E. Endometrial carcinoma: assessment of myometrial invasion with plain and gadolinium-enhanced MR imaging. J Magn Reson Imaging. 2000;12:460–6.

    Article  CAS  PubMed  Google Scholar 

  60. Nakao Y, Yokoyama M, Hara K, Koyamatsu Y, Yasunaga M, Araki Y, Watanabe Y, Iwasaka T. MR imaging in endometrial carcinoma as a diagnostic tool for the absence of myometrial invasion. Gynecol Oncol. 2006;102:343–7.

    Article  PubMed  Google Scholar 

  61. Gilbert C. Retinopathy of prematurity: a global perspective of the epidemics, population of babies at risk and implications for control. Early Hum Dev. 2008;84:77–82.

    Article  PubMed  Google Scholar 

  62. Schaffer DB, Palmer EA, Plotsky DF, Metz HS, Flynn JT, Tung B, Hardy RJ. Prognostic factors in the natural course of retinopathy of prematurity. The Cryotherapy for Retinopathy of Prematurity Cooperative Group. Ophthalmology. 1993;100:230–7.

    Article  CAS  PubMed  Google Scholar 

  63. Good WV, Hardy RJ, E.M.S. Group. The multicenter study of early treatment for retinopathy of prematurity (ETROP). New York: Elsevier; 2001.

    Google Scholar 

  64. Yen KG, Hess D, Burke B, Johnson RA, Feuer WJ, Flynn JT. The optimum time to employ telephotoscreening to detect retinopathy of prematurity. Trans Am Ophthalmol Soc. 2000;98:145.

    PubMed  PubMed Central  CAS  Google Scholar 

  65. Richter GM, Williams SL, Starren J, Flynn JT, Chiang MF. Telemedicine for retinopathy of prematurity diagnosis: evaluation and challenges. Surv Ophthalmol. 2009;54:671–85.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Ying G-S, Quinn GE, Wade KC, Repka MX, Baumritter A, Daniel E, e-ROP Cooperative Group. Predictors for the development of referral-warranted retinopathy of prematurity in the telemedicine approaches to evaluating acute-phase retinopathy of prematurity (e-ROP) study. JAMA Ophthalmol. 2015;133:304–11.

    Article  PubMed  PubMed Central  Google Scholar 

  67. Ransohoff DF, Feinstein AR. Problems of spectrum and bias in evaluating the efficacy of diagnostic tests. N Engl J Med. 1978;299:926–30.

    Article  CAS  PubMed  Google Scholar 

  68. Begg CB, Greenes RA. Assessment of diagnostic tests when disease verification is subject to selection bias. Biometrics. 1983;39:207–15.

    Article  CAS  PubMed  Google Scholar 

  69. Zhou X-H. Maximum likelihood estimators of sensitivity and specificity corrected for verification bias. Commun Stat Theory Methods. 1993;22:3177–98.

    Article  Google Scholar 

  70. Zhou X-H. Correcting for verification bias in studies of a diagnostic test’s accuracy. Stat Methods Med Res. 1998;7:337–53.

    Article  CAS  PubMed  Google Scholar 

  71. Harel O, Zhou XH. Multiple imputation for correcting verification bias. Stat Med. 2006;25:3769–86.

    Article  PubMed  Google Scholar 

  72. De Groot J, Janssen KJ, Zwinderman AH, Moons KG, Reitsma JB. Multiple imputation to correct for partial verification bias revisited. Stat Med. 2008;27:5880–9.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yong Chen .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG, part of Springer Nature

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Liu, Y., Chen, Y. (2018). Avenues for Further Research. In: Biondi-Zoccai, G. (eds) Diagnostic Meta-Analysis. Springer, Cham. https://doi.org/10.1007/978-3-319-78966-8_20

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-78966-8_20

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-78965-1

  • Online ISBN: 978-3-319-78966-8

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics